Th17 cells and IL-17 A—Focus on immunopathogenesis and immunotherapeutics

van den Berg, W.B. and McInnes, I.B. (2013) Th17 cells and IL-17 A—Focus on immunopathogenesis and immunotherapeutics. Seminars in Arthritis and Rheumatism, 43(2), pp. 158-170. (doi: 10.1016/j.semarthrit.2013.04.006) (PMID:24157091)

Abstract

Importance: Accumulating evidence suggests that IL-17 A has broad pathogenic roles in multiple autoimmune and immune-mediated inflammatory diseases, including psoriasis and rheumatoid arthritis (RA). The development of new therapies that inhibit IL-17 pathway signaling is of clinical significance.<p></p> Objectives: This review aims to summarize the current preclinical evidence on the role of Th17 cells and IL-17 and related cytokines in immune-mediated disease pathophysiology, with a focus on psoriasis and rheumatoid arthritis, as well as to summarize recent clinical trials in these indications with newly developed IL-17 pathway inhibitors.<p></p> Methods: A systematic literature search was conducted of PubMed using relevant keywords. Studies were assessed according to recent relevance to IL-17-mediated pathophysiology and clinical IL-17 inhibition. Experimental animal models of autoimmune disease and clinical studies that focused on IL-17 pathway inhibitors were included.<p></p> Results: Preclinical studies suggest that IL-17A is an attractive therapeutic target. Several IL-17A inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibodies, secukinumab and ixekizumab, and the anti-17RA monoclonal antibody brodalumab. Each has shown variable and sometimes favorable results in proof-of-concept and phase II clinical trials and is currently undergoing further clinical evaluation in a range of immune-mediated diseases.<p></p> Conclusion: Targeting the IL-17 pathway shows promise as strategy to treat immune-mediated diseases ranging from skin to joints.<p></p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain
• Authors: van den Berg, W.B., and McInnes, I.B.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Seminars in Arthritis and Rheumatism
• ISSN: 0049-0172
• ISSN (Online): 1532-866X